Global cocaine intoxication research trendsduring 1975–2015: a bibliometric analysisof Web of Science publicationsSa’ed H. Zyoud1,2*, W. Stephen Waring3, Samah W. Al-Jabi2 and Waleed M. Sweileh4
Abstract
Background: Cocaine is subject to recreational abuse as a stimulant and psychoactive agent, which poses a majorworldwide health problem. The aim of the present study was to perform a bibliometric analysis of publicationrelated to cocaine intoxication an insight of the research trends at a global level to enable recommendations forfuture research strategies in this field.
Methods: Publications about cocaine intoxication were retrieved from the Web of Science (WoS) Core Collectiondatabase on December 28, 2016, and analysed regarding the following bibliometric indicators: research trends,document types, languages, countries/territories with their h-index, collaboration patterns, journals with theirimpact factors (IF), and institutions.
Results: In total, 2,902 scientific publications from 1975 to 2015 were retrieved from the WoS database. The annualnumber of publications related to cocaine toxicity increased slightly after 1990 and reached a peak of 148 in 1992,with an average of 103 publications per year. The USA outranked other countries/territories with 2,089 publications,of which 1,927 arose exclusively from the USA and 162 involved international collaborations. The h-index forall publications related to cocaine was 212, and the h-index for all publications related to cocaine intoxicationwas 99. Moreover, the USA had the highest h-index of 95, followed by Spain with h-index of 24, and Canadawith h-index of 24. The main research topics were consistently reproductive toxicity, clinical management ofacute cocaine exposure, laboratory methods for detection of exposure to cocaine, cocaine metabolism, andcocaine toxicity in animals.
Conclusions: This is the first bibliometric approach to examining research related to cocaine toxicity and shows thatresearch activity has become more global and extensive since 1990. The USA remains the leading country regardingpublished literature, the highest h-index, and greatest role in international collaborations.
Keywords: Cocaine, Intoxication, Bibliometric, Web of Science
BackgroundCocaine is subject to recreational abuse as a stimulantand psychoactive agent, and it is commonly presented inits hydrochloride form as a white, water-soluble powder,and may be used orally, intravenously or by nasal insuffla-tion. Relatively pure formulations that lack a hydrochlor-ide moiety are presented in a crystalline form, so-called
‘freebase’ or ‘crack’ cocaine, which may be used by nasalinsufflation, smoking, ingestion or intravenous injection.Pharmaceutical cocaine preparations are available incountries that permit its use for medicinal purposes,namely as a local anaesthetic agent or to assist in man-aging epistaxis [1, 2].Peak circulating cocaine concentrations occur almost
immediately after intravenous injection and within sev-eral minutes of smoking, and may be delayed for up to1 h after nasal insufflation. Cocaine is rapidly eliminated,with a half-life is around one hour and reported durationof acute effects between 2 and 4 h [2]. People who ingest
* Correspondence: [email protected]; [email protected] Control and Drug Information Center (PCDIC), College of Medicineand Health Sciences, An-Najah National University, Nablus 44839, Palestine2Department of Clinical and Community Pharmacy, College of Medicine andHealth Sciences, An-Najah National University, Nablus 44839, PalestineFull list of author information is available at the end of the article
cocaine may often be considered in two categories: body“stuffers” and body “packers”. Body stuffers may ingestmoderate quantities of cocaine, often loosely packagedand, for example, ingested impulsively to avoid detec-tion. Body packers typically ingest very large quantitiesof cocaine contained in multiple well wrapped packagesfor the purposes of drug smuggling. Body stuffers andbody packers are at risk of systemic cocaine toxicity, andthere may be severe or fatal poisoning due to gastro-intestinal absorption after disruption of packed cocainewrapping [3–6].Pharmacological mechanisms of cocaine include block-
ade of sodium and potassium channels within the centralnervous system, excess sympathetic autonomic outflow,and direct alpha adrenoceptor-mediated vasoconstrictionof peripheral blood vessels [7]. Cocaine increases the riskof thrombotic and non-thrombotic acute coronary syn-drome, stroke and arterial dissection and regular usershave more advanced atherosclerosis than age-matchedcontrols; cardiotoxicity is enhanced in users that co-ingestethanol due to formation of cocaethylene [8]. These ad-verse effects include tachycardia, hypertension, chest pain,myocardial infarction, aortic and coronary artery dissec-tion, QT prolongation due to potassium channel blockade,and arrhythmia including ventricular fibrillation [9, 10].Other effects include sweating, fever, rhabdomyolysis,delirium, seizures, intracranial haemorrhage, and sero-tonin syndrome.Powders and other chemicals are often added to in-
crease bulk, including lidocaine, benzocaine, levamisole,baking flour, talc and washing powder, and microbialcontaminants may also be present [11]. The observed ef-fects may be caused by cocaine directly, or arise as anadverse effect of cutting agents or other contaminants.For example, agranulocytosis has been attributed to thepresence of levamisole [12], and methaemoglobinaemiahas been caused by local anaesthetic agents [13].Clinical management of cocaine intoxication is sup-
portive, including administration of benzodiazepines andhigh doses may be required to reduce agitation, treat sei-zures, and to allow control of tachycardia and highblood pressure. Fluid and electrolyte imbalance shouldbe corrected and serial electrocardiographs and cardiacmonitoring to assess for underlying myocardial ischae-mia or dysrhythmia. Standard treatment for suspectedcardiac ischaemia or myocardial infarction should beconsidered, namely antiplatelet agents, calcium channelblockers, nitrates, anticoagulants, and coronary arteriog-raphy [14, 15]. Intralipid may be considered for severe,life-threatening cardiac arrhythmia although too fewdata exist to fully understand its potential role in man-agement of cocaine toxicity [16]. There has been contro-versy regarding the use of lidocaine due to its sodiumchannel blocking effects that might be expected to
worsen cocaine cardiotoxicity; however, lidocaine maydisplace cocaine from cardiac sodium channels and re-duce arrhythmia risk [17]. Beta-blockers are generallyavoided as first line therapy because these will allow un-opposed alpha adrenoceptor-mediated vasoconstriction,and should normally be used with caution after an alphaadrenoceptor blocker has been introduced [18].At a global level, recreational cocaine use is at historically
high levels [19–21]. Emerging trends demonstrate that co-caine use is having societal and health consequences. Biblio-metric analysis is an efficient tool for examining trends indifferent scientific fields [22–26], and defined as the use ofstatistics and quantitative analysis for research output in theevaluation of research performance. Bibliometric networkanalysis allows analysis of research collaborations betweencountries, authors, and institutions [27–31].Recently, bibliometric techniques have been used to ex-
plore trends in research related to various scientific disci-plines; such as lab-on-a-chip research [32], nanotechnologyresearch [33], public health research [34], organic farmingresearch [35], pluripotent stem cell research [36], particu-late matter and atherosclerosis research [37], and Helico-bacter pylori research [38]. Earlier research has shown thatthe same methods may be applied to clinical toxicologythemes such as intravenous lipid emulsion as an antidote[39], methanol poisoning [40], and calcium channelblockers poisoning [41]. To our knowledge, there has beenno bibliometric study of research related to cocaine intoxi-cation. The present study sought to apply establishedbibliometric techniques to the field of cocaine toxicity, toallow the overall research trends to be examined from aglobal perspective, and to help build recommendation forfuture research opportunities.The study was designed to address the following ques-
tions: 1. What is the intellectual structure of the field ofresearch that deals with cocaine intoxication? 2. Whatare the domains or subject clusters that are identified inthis field, according to the terms used in publication ti-tles and abstracts? 3. What has been the evolution ofthis field of research over time? 4. What are the main re-search topics related to cocaine toxicity, and connectionsbetween them? 5. What are the networks of researchersidentified in the field, according to a co-authorship ana-lysis? 6. What are the institutional networks in this field?7. What are the main prolific journals, institutions,countries in this field? and, 8. Which publications havethe highest impact on this field?
MethodsData about cocaine intoxication were retrieved from theWeb of Science (WoS) Core Collection Database onDecember 28, 2016. This database is considered one ofthe most complete and reliable databases for bibliomet-ric analyses, and covers over 12,000 of the highest
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 2 of 15
impact, quality scientific international journals [42–46].To identify research related to cocaine intoxication, wetook the following steps in conducting this study:
Step 1: Publications with “cocaine” as keywords in thetitle were downloaded. To achieve better accuracy inthe results, the search was restricted to the Title fieldin the WoS database over all the previous year’s up toDecember 31, 2015 because if expanded to other searchfields such as Abstract or Keywords, many publicationsobtained were not relevant to cocaine (i.e false-positivedata). We applied a title-only search instead of a topicsearch (title, abstract, and keyword) accepting a smallloss of sensitivity but significantly increasing specificity[35, 47]. Year 2016 was excluded as this year still openfor new issues. Furthermore, data proposed to beincomplete due to reasons such as the time-lagbetween publications and indexing in WoS database.In this step it was promising to get all publications in thefield of cocaine intoxication that were published in theperiod comprised between 1975 and 2015.Step 2: We limited our retrieved publications in thefield of cocaine intoxication to all those indexed underthe research category ‘Toxicology” in WoS database.Step 3: To include all the documents about cocaineintoxication that are published in journals orconference proceedings indexed in other subjectcategories, we used the following search strategy: termcocaine in the title; using the truncated terms*toxic*OR poison* OR overdos* as a search phrases tosearch topic in the WoS database over all the earlieryears up to December 31, 2015. The search equationused produces publications that are relevant bytruncating some terms, such as “poison*”, which leadsto the recovery of publications on poison, poisoning, orpoisonous. Furthermore, in this step, we excludeddocuments published in the category “Toxicology”.Step 4: In this step, search equations from step 1, 2and 3 were combined in one search query and theresults were analyzed and presented. Search queryused for data extraction from WoS looked like this:(TI = (cocaine) AND TS = (*toxic* OR poison* ORoverdos*)) OR (TI = (cocaine) AND SU= (Toxicology));(See Additional file 1).Step 5: The retrieved publications were analysedregarding the following bibliometric indicators as donein previous bibliometric studies [27–31]: researchtrends, document types, languages, countries/territorieswith their h-index, collaboration patterns, journals withtheir impact factors (IF), and institutions. Our studyrelied on the connection between countries, topics,authors, and institutions using visualizations andclustering algorithms to locate the main groups amongthem by VOSviewer software [27, 48–50]. The
VOSviewer v.1.6.5 was used for viewing andconstructing the desired bibliometric maps [48].VOSviewer was employed to illustrate the co-occurrence network of high-frequency terms related tococaine toxicity to detect how research topics relatedto cocaine changed and progressed through time. Thetimespan of 1975–2015 was selected, and it was splitinto three periods: 1975–1995; 1996–2005, and 2006–2015. The size of circles in VOSviewer maps representsthe number of publications related to certain term,and the distance between two terms gives an implicationof the number of co-occurrences of the terms.Furthermore, terms close to each other or havingcertain color are more probable dealing with thesame topic.
Statistical analysisAll the retrieved results were imported into Excel 2007for further analysis, and data presented as frequenciesand percentages of publications. The ten most product-ive countries and journals in the field of cocaine toxicitywere identified. The journal IF was obtained from theJournal Citation Report (JCR) Science Edition 2015. Theh-index was calculated as the number of publications (n)that have achieved at least n citations. Publications ori-ginating from England, Northern Ireland, Scotland, andWales were merged as being from the United Kingdom(UK). Pearson correlation test was used to examine thecorrelations between all cocaine publication productivityand that related to specifically to cocaine toxicity. A sig-nificance level of P < 0.05 was considered to be statisti-cally significant. SPSS ® version 16 was used to performthe statistical analysis.
Fig. 1 Evolution of scientific research in the field of cocaine toxicity
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 3 of 15
ResultsFrom 1975 to 2015, there were 21,683 publications oncocaine, including 2,902 scientific publications related tococaine intoxication (See Additional file 1). Out of the2,902 publications in the field of cocaine toxicity thatwere analysed in this study, 2,823 (97.3%) were pub-lished in English, followed by Spanish (36; 1.2%), French(29; 1.0%) and German (12; 0.4%). Original articles(2,205) were the most frequent publication type (76.0%),followed by meeting abstracts (323; 11.1%), proceedings
papers (145, 5.0%), reviews (142; 4.9%), and letters (108;3.7%). Annual publications on cocaine toxicity are sum-marised in Fig. 1. The annual number of publications re-lated to cocaine toxicity increased slightly after 1990 andreached a peak of 148 publications in 1992, and then thetotal output has fluctuated with an average of 103 publi-cations per year. Publication of articles related to cocainein all fields has increased considerably after 1986 with apeak of 825 in 1996, and a subsequent average of 746publications per year. There was a strong correlation
Table 1 Top ten most productive countries in the field of cocaine toxicity
SCR Country Number ofdocuments (%)
Average citationsper document
h-index No. of collaborativecountries
No. of publications fromcollaboration
1st USA 2089 (71.99) 25.15 95 38 162
2nd Spain 145 (5.00) 13 24 14 30
3rd Italy 100 (3.45) 15.12 23 10 28
4th Canada 92 (3.17) 24.83 24 9 31
5th France 90 (3.10) 14.31 21 13 30
6th UK 80 (2.76) 32.33 23 13 32
7th Brazil 55 (1.90) 8.32 12 8 16
8th Germany 50 (1.72) 14.34 18 10 17
9th Japan 42 (1.45) 13.19 14 1 9
10th Switzerland 31 (1.07) 20.19 14 6 9
Fig. 2 Network visualization map of country co-authorships. Of the 60 countries, 32 had at least five publications; the largest set of connectedcountries consists of 31 countries in 12 clusters
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 4 of 15
between publication productivity related to cocaine inall fields and productivity related to cocaine toxicity(r = 0.929; p-value < 0.001).Table 1 shows the leading countries/territories, ranked
by number of publications. The USA outranked othercountries/territories with 2,089 publications, of which1,927 were exclusively produced in the USA and 162were international collaborations. Spain published thesecond highest number of total publications with 145publications, followed by Italy with 100 publications,Canada with 92 publications, and France with 90 publi-cations. The h-index for all publications related to co-caine was 212, and the h-index for all publicationsrelated to cocaine intoxication was 99. Moreover, theUSA had the highest h-index of 95, followed by Spainwith h-index of 24, and Canada with h-index of 24. Thehighest average number of citations was for publicationsarising from the UK (32 citations), followed by the USA(25 citations), and Canada (25 citations).Figure 2 illustrates the collaboration network of coun-
tries publishing more than five documents. The size ofcircles represents the number of publications of thecountry and the thickness of lines signifies the size ofcollaboration. The USA had the most collaborationwith other worldwide countries. A co-authorship mapdemonstrated that the top active authors in the fieldof cocaine intoxication were present in 13 differentclusters (Fig. 3).The ten most productive of journals/periodicals in
the field of cocaine toxicity are listed in Table 2.
Neurotoxicology and Teratology published the mostcocaine articles (274; 9.4%), followed by Journal ofAnalytical Toxicology (215; 7.4%), Clinical Toxicology(79; 2.7%), and Journal of Pharmacology and Experi-mental Therapeutics (64; 2.2%). The top ten most pro-ductive journals accounted for 33.5% of the totalpublications. The highest IF was associated with An-nals of Emergency Medicine (IF = 5.008). Figures 4, 5,and 6 illustrate the co-occurrence networks for high-frequency terms related to cocaine toxicity in the
Fig. 3 Network visualization map of the authors, 1975–2015. Of the 7,820 authors, 313 had at least five publications; the largest set of connectedauthors consists of 99 authors in 13 clusters
Table 2 Ten most active journals in the field of cocaine toxicity
SCR Journal/Periodical Number ofdocuments (%)
IFa
1st Neurotoxicology and Teratology 274 (9.44) 2.488
2nd Journal of Analytical Toxicology 215 (7.41) 2.322
3rd Clinical Toxicology 79 (2.72) 2.886
4th Journal of Pharmacology andExperimental Therapeutics
64 (2.21) 3.760
5th Drug and Alcohol Dependence 60 (2.07) 3.349
6th Annals of Emergency Medicine 52 (1.79) 5.008
6th Journal of Forensic Sciences 52 (1.79) 1.322
8th Toxicology Letters 50 (1.72) 3.522
9th Pharmacology Biochemistry and Behavior 48 (1.65) 2.537
10th Life Sciences 39 (1.34) 2.685
10th Psychopharmacology 39 (1.34) 3.540
SCR Standard competition ranking, IF Impact factoraThe impact factor was reported according to journal citation reports(JCR) 2015
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 5 of 15
Fig. 4 High-frequency terms in the titles and abstracts of cocaine toxicity publications during 1975–1995 with research topics indicated.Of the 11,752 terms, 303 terms occurred at least ten times. For each of the 303 terms, a relevance score was calculated and used toselect the 60% most relevant terms. The largest set of connected terms consists of 182 terms in four clusters. (Number of publicationsrelated to cocaine intoxication = 954)
Fig. 5 High-frequency terms in the titles and abstracts of cocaine toxicity publications during 1996–2005 with research topics indicated.Of the 17,767 terms, 451 terms were used at least ten times. For each of the 451 terms, a relevance score was calculated, and used toselect the 60% most relevant terms. The largest set of connected terms consists of 271 terms in five clusters. (Number of publicationsrelated to cocaine intoxication = 987)
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 6 of 15
Fig. 6 High-frequency terms in the titles and abstracts of cocaine toxicity publications during 2006–2015 with research topics indicated.Of the 16,914 terms, 440 terms were used at least ten times. For each of the 440 terms, a relevance score was calculated, and used toselect the 60% most relevant terms. The largest set of connected terms consists of 264 terms in four clusters. (Number of publicationsrelated to cocaine intoxication = 961)
Fig. 7 High-frequency terms in the titles and abstracts of cocaine toxicity publications during 1975–2015 with research topics indicated.Of the 38,273 terms, 1,135 terms occurred at least ten times. For each of the 1,135 terms, a relevance score was calculated, and used toselect the 60% most relevant terms. The largest set of connected terms consists of 681 terms in five clusters. (Number of publicationsrelated to cocaine intoxication = 2,902)
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 7 of 15
Table
3Topthreecitedpu
blications
inthefield
ofcocainetoxicity
forthetop10
mostprod
uctivecoun
tries
SCR
Autho
rsTitle
Year
ofpu
blication
Source
title
IFa
Citedby
Average
citatio
nspe
ryear
USA 1s
tRamam
oorthy
etal[55]
Antidep
ressant-andcocaine-sensitive
human
serotonintransporter:molecular
clon
ing,
expression
,and
chromosom
allocalization
1993
Proceeding
sof
theNationa
lAcadem
yof
Sciences
9.423
657
27.38
2nd
Grant
etal.[52]
Activationof
mem
orycircuitsdu
ring
cue-elicitedcocainecraving
1996
Proceeding
sof
theNationa
lAcadem
yof
Sciences
9.423
636
30.29
3rd
McFarland
etal.[74]
Limbicandmotor
circuitryun
derlying
footshock-indu
cedreinstatem
entof
cocaine-seekingbe
havior
2004
Journa
lofN
euroscience
5.924
304
23.38
Spain
1st
Farreet
al.[53]
Alcoh
olandcocaineinteractions
inhu
mans
1993
Journa
lofP
harm
acologyan
dExperim
entalTherapeutics
3.760
133
5.54
2nd
Farreet
al.[59]
Cocaine
andalcoho
linteractio
nsin
humans:
neuroe
ndocrin
eeffectsand
cocaethylene
metabolism
1997
Journa
lofP
harm
acologyan
dExperim
entalTherapeutics
3.760
693.45
3rd
Orteg
a-Carnicer
etal.[51]
Abo
rted
sudd
ende
ath,transien
tBrug
ada
pattern,andwideQRS
dysrrhythm
iasafter
massive
cocaineinge
stion
2001
Journa
lofElectrocardiology
1.290
633.94
Italy 1s
tTagliaro
etal.[58]
Capillaryelectrop
horesisfortheinvestigation
ofillicitdrug
sin
hair:de
term
inationof
cocaine
andmorph
ine
1993
Journa
lofC
hrom
atograph
yA
3.926
712.96
2nd
Add
iset
al.[68]
Fetaleffectsof
cocaine:an
updatedmeta-analysis
2001
ReproductiveToxicology
2.850
654.06
3rd
Cervo
etal.[77]
ProteinkinasesAandCareinvolved
inthe
mechanism
sun
derlyingconsolidationof
cocaine
placecond
ition
ing
1997
BrainResearch
2.561
582.90
Canada
1st
BozarthandWise[79]
Toxicityassociated
with
long
-term
intravenou
sheroinandcocaineself-administratio
nintherat
1985
JAMA:
Journa
lofthe
American
MedicalAssociation
37.684
169
5.28
2nd
NanjiandFilipen
ko[56]
Asystoleandventricular
fibrillatio
nassociated
with
cocaineintoxicatio
n1984
Chest
5.94
169
5.12
3rd
Tynd
aleet
al.[75]
Neuronalcytochrom
eP450IID
1(deb
risoq
uine
/sparteine-type
):po
tent
inhibitio
nof
activity
by(-)-cocaine
andnu
cleo
tidesequ
ence
iden
tity
tohu
man
hepatic
P450
gene
CYP2D
6
1991
Molecular
Pharmacology
3.931
143
5.50
France
1st
Leno
iret
al.[73]
IntenseSw
eetnessSurpassesCocaine
Reward
2007
PLOSONE
3.057
162
16.20
2nd
Mauriceet
al.[78]
2002
Neuroscience&Biobehavioral
Review
s8.580
103
6.87
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 8 of 15
Table
3Topthreecitedpu
blications
inthefield
ofcocainetoxicity
forthetop10
mostprod
uctivecoun
tries(Con
tinued)
Sigm
a(1)(sigma(1))receptorantagon
istsrepresent
anewstrategy
againstcocaineaddictionand
toxicity
3rd
Pelline
net
al.[62]
CocaineN-dem
ethylatio
nandthemetabolism
-related
hepatotoxicitycanbe
preventedby
cytochrome
P450
3Ainhibitors
1994
European
JournalofPharm
acology
2.730
753.26
UK 1s
tIto
etal.[64]
Differentialcon
trolover
cocaine-seekingbehavior
bynu
cleusaccumbens
core
andshell
2004
NatureNeuroscience
16.724
269
2nd
Whitelaw
etal.[67]
Excitotoxiclesion
sof
thebasolateralamygdala
impairtheacqu
isition
ofcocaine-seeking
behaviou
run
derasecond
-order
sche
duleof
reinforcem
ent
1996
Psycho
pharmacology
3.540
244
3rd
Voreletal.[66]
Dop
amineD-3
receptor
antago
nism
inhibits
cocaine-seekingandcocaine-en
hanced
brain
reward
2002
Journa
lofN
euroscience
5.924
200
Brazil
1st
Masur
etal.[72]
Increasedstim
ulatoryeffect
bythecombine
dadministrationof
cocaineandalcoho
linmice.
1989
Alcoho
l2.440
361.29
2nd
Crouchet
al.[54]
Analysisof
cocaineandits
metabolitesfro
mbiolog
icalspecim
ensusingsolid-phase
extractio
nandpo
sitiveionchem
icalionizatio
nmass
spectrom
etry
1995
Journa
lofA
nalyticalToxicology
2.322
341.55
3rd
Lepsch
etal.[61]
Cocaine
indu
cescellde
athandactivates
the
transcrip
tionnu
clearfactorkappa-b
inpc12
cells
2009
Molecular
Brain
3.745
303.75
Germany
1st
Wilbert-Lampe
net
al.[60]
Cocaine
increasestheen
dothelialrelease
ofim
mun
oreactiveend
othe
linandits
concen
trations
inhu
man
plasmaandurine-R
eversalbycoincubation
with
sigma-receptor
antago
nists
1998
Circulation
17.047
693.63
2nd
Maureret
al.[80]
Toxicokineticsof
drug
sof
abuse:Cu
rrentknow
ledg
eof
theiso
enzymes
involved
inthehu
man
metabolism
oftetrahydrocann
abinol,cocaine,heroin,
morph
ine,andcodeine
2006
Therapeutic
DrugMon
itoring
2.094
676.09
3rd
Bren
zVerca
etal.[65]
Distributionof
alph
a-andgamma-synu
cleins
intheadultratbrainandtheirmod
ificatio
nby
high
-dosecocainetreatm
ent
2003
European
Journa
lofN
euroscience
2.975
402.86
Japan
1st
Nakaharaet
al.[69]
Hairanalysisfordrug
sof
abuse.V.Thefacilityin
incorporationof
cocaineinto
hairover
itsmajor
metabolites,be
nzoylecgon
ineandecgo
nine
methylester
1992
Archives
ofToxicology
6.637
692.76
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 9 of 15
Table
3Topthreecitedpu
blications
inthefield
ofcocainetoxicity
forthetop10
mostprod
uctivecoun
tries(Con
tinued)
2nd
Aokietal.[63]
Cocaine
-indu
cedliver
injury
inmiceismed
iated
bynitricoxideandreactiveoxygen
species
1997
European
JournalofPharm
acology
2.730
452.25
3rd
NakaharaandKikura
[70]
Hairanalysisfordrug
sof
abuse.VII.The
incorporationratesof
cocaine,be
nzoylecgon
ine
andecgo
nine
methylester
into
rathairand
hydrolysisof
cocainein
rathair
1994
Archives
ofToxicology
6.637
431.87
Switzerland
1st
BoelsterliandGoldlin
[57]
Biom
echanism
sof
cocaine-indu
cedhe
patocyte
injury
med
iatedby
theform
ationof
reactive
metabolites
1991
Archives
ofToxicology
6.637
953.65
2nd
Boelsterliet
al.[71]
Iden
tificationof
cytochromeP-450IIB1as
acocaine-bioactivatingisoform
inrathe
patic
microsomes
andin
cultu
redrathe
patocytes.
1992
DrugMetabolism
&Disp
osition
3.210
622.48
3rd
Boelsterliet
al.[76]
Oxyge
nfre
eradicalp
rodu
ctionmed
iatedby
cocaineandits
ethano
l-derived
metabolite,
cocaethylene
,inrathe
patocytes.
1993
Hepatology
11.711
542.25
SCRStan
dard
compe
titionrank
ing,
IFIm
pact
factor
a The
impa
ctfactor
was
repo
rted
accordingto
journa
lcita
tionrepo
rts(JCR)
2015
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 10 of 15
titles and abstracts of the publications between 1975–1995, 1996–2005, and 2006–2015, respectively. Figure 7shows the co-occurrence network of high-frequency termsin the title or/and abstract of retrieved publications relatedto cocaine toxicity during 1975–2015 which reflect mostfrequently encountered topics in this field. The fivemost used topics in cocaine toxicity are represented byfive coloured clusters: blue, yellow, green, purple andred colors. Cluster number 1 (yellow color) includedterms related to reproductive toxicity topic such as“prenatal cocaine exposure”, “infant”, or “mother”;Cluster number 2 (green color) included terms relatedto cocaine exposure and clinical management topicsuch as “patient”, “case”, or “hospital”; Cluster number3 (purple color) included terms related to laboratorymethods for detection of exposure to cocaine topicsuch as “mass spectrometry”, “metabolite”, or “detec-tion”; Cluster number 4 (blue color) included terms re-lated to cocaine metabolism topic such as “enzyme”,“inducer”, or “metabolism”; and Cluster number 5 (redcolor) included terms related to cocaine toxicity in animalmodels topic such as “rat”, “mice”. Additional file 2: FigureS1–S4 shows the density maps for co-occurrence of termsused in the title and abstract of retrieved publicationsacross different time periods, from low density (blue) tohigh density (red).The three most cited publications in cocaine toxicity
are shown for each of the top ten productive countries(Table 3) [51–80]. From 1975 to 2015, the most fre-quently cited article was published in Proceedings of theNational Academy of Sciences by Ramamoorthy et al[55] in 1993 and had been cited 657 times. Table 4 liststhe top three most productive institutions from orcollaborating with the top ten most productive coun-tries in the field of cocaine toxicity. Leading was theNational Institute on Drug Abuse (NIDA) with 115publications, followed by University of Miami with 65publications. Figure 8 demonstrates the collaborationnetwork of top-155 institutes publishing more thanfive documents during 1975–2015. The size of circlesrepresents the number of publications of the instituteand the thickness of lines signifies the size of collaboration.As shown in Fig. 8, National Institute on Drug Abuse(NIDA), University of Miami, and Tufts University have themost collaboration with other USA or worldwide institutes.
DiscussionThe number of publications in the field of cocaine in-toxication has grown during the studied 40 years, andcorrelates with growth in publications in all fields relatedto cocaine. There was a steady growth rate until 1992,then total output has been fairly stable with some fluctu-ations between 1992 and 2015. The increased number ofpublications may be due to: 1. the number of frequent
Table 4 Top three most productive institutions from orcollaborating with the top ten most productive countries inthe field of cocaine toxicity
SCR Institute n (%)
USA (number of documents = 2,089)
1st National Institute on Drug Abuse (NIDA) 115 (5.51)
2nd University of Miami 65 (3.11)
3rd Yale University 55 (2.63)
Italy(number of documents = 100)
1st UniversitàCattolica del Sacro Cuore 12 (12.00)
2nd IstitutoSuperiore di Sanità 9 (9.00)
3rd Sapienza – Università di Roma 8 (8.00)
France(number of documents = 90)
1st HôpitalFernand-Widal 15 (16.67)
2nd Institut national de la santé et de larecherchemédicale-INSERM
9 (10.00)
3rd Columbia University College of Physiciansand Surgeons
7 (7.78)
Brazil(number of documents = 55)
1st University of São Paulo 22 (40.00)
2nd Universidade Federal de Minas Gerais 6 (10.91)
3rd Universidade Federal de São Paulo 6 (10.91)
Japan(number of documents = 42)
1st Kyoto University 9 (21.43)
2nd Showa University 6 (14.29)
3rd National Institute on Drug Abuse (NIDA) 4 (9.52)
Spain (number of documents = 145)
1st University of Santiago de Compostela 15 (10.35)
2nd Autonomous University of Barcelona 11 (7.59)
3rd University of Valencia 9 (6.21)
Canada(number of documents = 92)
1st University of Toronto 28 (30.44)
2nd The Hospital for Sick Children 24 (26.09)
3rd University of British Columbia 8 (8.70)
UK(number of documents = 80)
1st University of Cambridge 18 (22.50)
2nd Guy’s and St Thomas’ NHS Foundation Trust 6 (7.50)
3rd Guy’s Hospital 4 (5.00)
Germany(number of documents = 50)
1st Goethe University Frankfurt 4 (8.00)
2nd Maastricht University 4 (8.00)
3rd Universität Heidelberg 4 (8.00)
Switzerland(number of documents = 31)
1st University of Zurich 12 (38.71)
2nd Swiss Federal Institute of Technology 10 (32.26)
3rd Université de Fribourg 2 (6.45)
n Number of documents (%), SCR Standard competition ranking
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 11 of 15
cocaine users has been increasing since 1980 [81], 2.greater awareness of concerns about life-threatening conse-quences of cocaine toxicity, particularly related to cardiac,cerebrovascular, and maternal morbidity and mortality[2, 82, 83], 3. increasing cocaine use at a global level [84],and, 4. new pharmacological concepts related to cocaineuse, namely in its role as a local anaesthetic agent [81, 85].The USA is the most productive country in research
related to cocaine intoxication, which is similar to pat-terns identified for other clinical toxicology research,such as intravenous lipid emulsion as an antidote [39],paracetamol poisoning [86, 87], acetylcysteine as anti-dote [88], methanol poisoning [40], and calcium channelblockers poisoning [41]. Possible reasons include thecomparatively large research budgets, and rapid eco-nomic growth [89]. In addition, it was reported that co-caine was the most commonly abused drug in parts ofthe USA [1, 19]. Another noticeable finding was that allthe top cited publications in the field of cocaine intoxi-cation originated from the USA. These results are con-sistent with data obtained by previous bibliometricstudies that a few developed countries such as the USAgenerate the most frequently cited toxicology studies[39, 41, 87, 90]. This might be influenced by factors suchas access to publications by scholars from the USA.There may be greater opportunities for USA researchersto access databases and attend international conferencesand academic exchange programs, that contribute to
higher citation rates [91]. A possible explanation is thegeneralised trend towards increasing publication numbersacross a range of scientific fields within the USA. Further-more, there are some indications that the USA researcherstend to cite publications from their own country [92].The percentages of all publications appearing in the
top journals were comparatively low, indicating a spreadof publications allocated to generalised and specialisedjournals, and reflecting the broad range of research in-terests related to cocaine. This is similar to several otherareas of toxicology research with a high level of multi-disciplinary interest, including intravenous lipid emul-sion as an antidote [39], methanol poisoning [40], andcalcium channel blockers poisoning [41].The most frequently cited and highly influential publi-
cation was related to a novel hypothesis of cocainepharmacological action, namely “Antidepressant- andcocaine-sensitive human serotonin transporter: molecularcloning, expression, and chromosomal localization”. Under-standing the citation patterns is important in evaluating anindividual publication, and may also help understand how acertain topics or concepts are disseminated within thescientific community [93].Bibliometric analysis has a limitations, including database
variations, discipline variation, and bias towards Englishlanguage [26, 94]. As with all previous bibliometric studies[94–96], our study is limited by use of search term “co-caine” to only the title search. Specially, any publications
Fig. 8 Institutional collaboration networks in cocaine toxicity during 1975–2015. Of the 1,533 institutes, 171 had at least five relevant publications.The largest set of connected institutes consists of 155 institutes in 18 clusters
Zyoud et al. Substance Abuse Treatment, Prevention, and Policy (2017) 12:6 Page 12 of 15
that used “cocaine” as a key word in the publication mayhave been missed in our analysis. It is widely known thatthe total number of publications from major databases suchas Google Scholar, Scopus, PubMed, and WoS differs. Fur-thermore, there is an indisputable inclination that English isthe language of science, and certain databases may omitpublications in different languages.
ConclusionsResearch progress related to cocaine intoxication hasbeen assessed for the first time based on a bibliometricapproach. Research related to cocaine intoxication hasbecome more global and extensive after 1990, and theUSA is the leading country with the greatest number ofpublications and highest h-index. The main topics haveconsistently been reproductive toxicity, cocaine exposureand clinical management, laboratory methods for detec-tion of exposure to cocaine, cocaine metabolism, and co-caine toxicity in animals. These findings may provide avaluable basis for identifying important topics for futureresearch, and create opportunities for collaboration be-tween research groups with complementary scientificinterest in the field of cocaine toxicity.
Additional files
Additional file 1: Methodology used to retrieve publications related tococaine intoxication for analysis using Web of Science (WoS) Core CollectionDatabase. (DOCX 17 kb)
Additional file 2: Density view of terms map based on the co-occurrencematrix of terms from text data in the title and abstract of retrieved publicationsrelated to cocaine toxicity by periods. Figure S1. Density view of terms mapin Period I (1975–1995); colors show the density of relevance, sorting fromblue (lowest density) to red (highest density). (number of publications relatedto cocaine intoxication = 954). Figure S2. Density view of terms map in PeriodII (1996–2005); colors show the density of relevance, sorting from blue (lowestdensity) to red (highest density). (Number of publications related to cocaineintoxication = 987). Figure S3. Density view of terms map in Period III(2006–2015); colors show the density of relevance, sorting from blue(lowest density) to red (highest density). (Number of publications related tococaine intoxication = 961). Figure S4. Density view of terms map in Period1975–1995; colors show the density of relevance, sorting from blue (lowestdensity) to red (highest density). (Number of publications related to cocaineintoxication = 2,902). (DOCX 794 kb)
AbbreviationsIFs: Impact factors; JCR: Journal Citation Reports; SCR: Standard CompetitionRanking; WoS: Web of Science
AcknowledgementsSpecial thanks to WHO’s Health InterNetwork Access to Research Initiative(HINARI), and An-Najah National University for giving the opportunities toaccess most recent information sources such as WoS database.
FundingNo funding was received for writing this study.
Availability of data and materialsNot applicable.
Authors’ contributionsSZ, SA, WS and WW were involved in the study conception and the studydesign. SZ, data collection, wrote the first draft and conducted the analysis. SA,WS and WW contributed to the writing and critically revising the article. Allauthors read and approved the final manuscript and agreed on its submission.
Competing interestsThe authors declare that they have no competing interests.
Consent for publicationNot applicable.
Ethics approval and consent to participateNot applicable.
Author details1Poison Control and Drug Information Center (PCDIC), College of Medicineand Health Sciences, An-Najah National University, Nablus 44839, Palestine.2Department of Clinical and Community Pharmacy, College of Medicine andHealth Sciences, An-Najah National University, Nablus 44839, Palestine.3Acute Medical Unit, York Teaching Hospitals NHS Foundation Trust,Wigginton Road, York YO31 8HE, UK. 4Department of Pharmacology andToxicology, College of Medicine and Health Sciences, An-Najah NationalUniversity, Nablus 44839, Palestine.
Received: 17 September 2016 Accepted: 1 February 2017
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